Resident Microbiota Affect Bordetella pertussis Infectious Dose and Host Specificity

Weyrich, Laura S.; Feaga, Heather A.; Park, Jihye; Muse, Sarah J.; Safi, Chetan Y.; Rolin, Olivier; Young, Sarah E.; Harvill, Eric T.

doi:10.1093/infdis/jit597

Cited by 44 publications

(48 citation statements)

References 44 publications

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“…In contrast, stable colonization of mice with B. pertussis , a human-adapted pathogen, required a more than 100-fold higher inoculum and still could not displace the indigenous flora. However, local antibiotic treatment to deplete commensal bacteria lowered the required infectious dose of B. pertussis to <100 colony-forming units; still, the presence of one species of mouse-commensal bacteria could inhibit B. pertussis colonization even in antibiotic-treated animals (131). At least one commensal bacterium has the ability to fight back against opportunistic colonizers.…”

Section: Modifiers: Host Competitors Coinfectionsmentioning

confidence: 99%

Mechanisms of Bacterial Colonization of the Respiratory Tract

Siegel¹,

Weiser²

2015

Annu. Rev. Microbiol.

167

123

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Respiratory tract infections are an important cause of morbidity and mortality worldwide. Chief among these are infections involving the lower airways. The opportunistic bacterial pathogens responsible for most cases of pneumonia can cause a range of local and invasive infections. However, bacterial colonization (or carriage) in the upper airway is the prerequisite of all these infections. Successful colonizers must attach to the epithelial lining, grow on the nutrient-limited mucosal surface, evade the host immune response, and transmit to a susceptible host. Here, we review the molecular mechanisms underlying these conserved stages of carriage. We also examine how the demands of colonization influence progression to disease. A range of bacteria can colonize the upper airway; nevertheless, we focus on strategies shared by many respiratory tract opportunistic pathogens. Understanding colonization opens a window to the evolutionary pressures these pathogens face within their animal hosts and that have selected for attributes that contribute to virulence and pathogenesis.

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Section: Modifiers: Host Competitors Coinfectionsmentioning

confidence: 99%

Mechanisms of Bacterial Colonization of the Respiratory Tract

Siegel¹,

Weiser²

2015

Annu. Rev. Microbiol.

167

123

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“…Jain et al (17) discovered functional and structural differences in the paranasal sinus epithelium between germfree and specific-pathogenfree mice, suggesting the importance of a healthy microbiota in normal epithelial development. In addition, the sinonasal microbial community can act as a colonization barrier to incoming microorganisms or prevent overgrowth of pathogenic species (18,19). Pathogenic species (16,20) encounter a diverse polymicrobial community present on the epithelium, which may facilitate or block their adherence and outgrowth.…”

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confidence: 99%

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Rudder

Calatayud

Lebeer

et al. 2020

mSphere

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The epithelium of the human sinonasal cavities is colonized by a diverse microbial community, modulating epithelial development and immune priming and playing a role in respiratory disease. Here, we present a novel in vitro approach enabling a 3-day coculture of differentiated Calu-3 respiratory epithelial cells with a donor-derived bacterial community, a commensal species (Lactobacillus sakei), or a pathobiont (Staphylococcus aureus). We also assessed how the incorporation of macrophage-like cells could have a steering effect on both epithelial cells and the microbial community. Inoculation of donor-derived microbiota in our experimental setup did not pose cytotoxic stress on the epithelial cell layers, as demonstrated by unaltered cytokine and lactate dehydrogenase release compared to a sterile control. Epithelial integrity of the differentiated Calu-3 cells was maintained as well, with no differences in transepithelial electrical resistance observed between coculture with donor-derived microbiota and a sterile control. Transition of nasal microbiota from in vivo to in vitro conditions maintained phylogenetic richness, and yet a decrease in phylogenetic and phenotypic diversity was noted. Additional inclusion and coculture of THP-1-derived macrophages did not alter phylogenetic diversity, and yet donor-independent shifts toward higher Moraxella and Mycoplasma abundance were observed, while phenotypic diversity was also increased. Our results demonstrate that coculture of differentiated airway epithelial cells with a healthy donor-derived nasal community is a viable strategy to mimic host-microbe interactions in the human upper respiratory tract. Importantly, including an immune component allowed us to study host-microbe interactions in the upper respiratory tract more in depth. IMPORTANCE Despite the relevance of the resident microbiota in sinonasal health and disease and the need for cross talk between immune and epithelial cells in the upper respiratory tract, these parameters have not been combined in a single in vitro model system. We have developed a coculture system of differentiated respiratory epithelium and natural nasal microbiota and incorporated an immune component. As indicated by absence of cytotoxicity and stable cytokine profiles and epithelial integrity, nasal microbiota from human origin appeared to be well tolerated by host cells, while microbial community composition remained representative for that of the human (sino)nasal cavity. Importantly, the introduction of macrophage-like cells enabled us to obtain a differential readout from the epithelial cells dependent on the donor microbial background to which the cells were exposed. We conclude that both model systems offer the means to investigate host-microbe interactions in the upper respiratory tract in a more representative way.

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“…During our in vitro analyses of B. bronchiseptica bfrA, bfrD, and/or bfrE single-or multiple-receptor mutants, we did not observe overproduction of the alcaligin siderophore or any other effects on siderophore-mediated iron uptake that may explain the apparent nasal fitness advantage. A recent study examined mouse nasal colonization efficacies of B. pertussis and B. bronchiseptica and showed significant species differences that involved the respiratory microbiota (54). B. bronchiseptica nasal colonization was obtained using infecting doses as low as 5 CFU, whereas much higher doses of B. pertussis (10,000 CFU) or antibiotic pretreatment was required to overcome inhibition by the microflora.…”

Section: Discussionmentioning

confidence: 99%

Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function

2015

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Bordetella bronchiseptica can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and although Bordetella pertussis has the bfrD and bfrE genes, the role of these genes in iron uptake has not been demonstrated. In this study, the bfrD and bfrE genes of B. pertussis were shown to be functional in B. bronchiseptica, but neither B. bronchiseptica bfrD nor bfrE imparted catecholamine utilization to B. pertussis. Gene fusion analyses found that expression of B. bronchiseptica bfrA was increased during iron starvation, as is common for iron receptor genes, but that expression of the bfrD and bfrE genes of both species was decreased during iron limitation. As shown previously for B. pertussis, bfrD expression in B. bronchiseptica was also dependent on the BvgAS virulence regulatory system; however, in contrast to the case in B. pertussis, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression of bfrD in B. bronchiseptica. Further studies using a B. bronchiseptica bvgAS mutant expressing the B. pertussis bvgAS genes revealed that the interspecies differences in bfrD modulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to the in vivo fitness of B. bronchiseptica and B. pertussis. Additional evidence of the in vivo importance of the B. pertussis receptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with the B. pertussis BfrD and BfrE proteins.

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Resident Microbiota Affect Bordetella pertussis Infectious Dose and Host Specificity

Cited by 44 publications

References 44 publications

Mechanisms of Bacterial Colonization of the Respiratory Tract

Mechanisms of Bacterial Colonization of the Respiratory Tract

Dual and Triple Epithelial Coculture Model Systems with Donor-Derived Microbiota and THP-1 Macrophages To Mimic Host-Microbe Interactions in the Human Sinonasal Cavities

Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function

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